Effects of uric acid on endothelial dysfunction in early chronic kidney disease and its mechanisms.

Wang Y, Bao X - Eur. J. Med. Res. (2013)

Bottom Line:
An increase in serum uric acid (UA) occurs during the early and middle stages of chronic kidney disease (CKD) and aggravates the deterioration of kidney function.Linear regression analysis showed that the level of serum UA had a significant positive correlation with serum endothelin-1 and the percentage of collagen I positive area, but a negative correlation with serum nitric oxide (NO) and NO/endothelin-1 ratio.In addition, the level of serum UA had significant positive correlations with serum malonaldehyde, serum C-reactive protein, serum oxidatively-modified low-density lipoprotein and serum low-density lipoprotein, but a negative correlation with serum superoxide dismutase.

Background: An increase in serum uric acid (UA) occurs during the early and middle stages of chronic kidney disease (CKD) and aggravates the deterioration of kidney function. This study aims to explore the relation between UA and endothelial dysfunction in early CKD and its mechanisms in a murine model.

Methods: The experimental animals were randomly divided into three groups (n = 10): sham-operation group (control group), right nephrectomy only group (CKD group) and right nephrectomy with oxonic potassium group (CKD with hyperuricemia group). Furthermore, we analyzed the relation between UA and endothelial dysfunction indices in early CKD as well as its mechanisms.

Results: Linear regression analysis showed that the level of serum UA had a significant positive correlation with serum endothelin-1 and the percentage of collagen I positive area, but a negative correlation with serum nitric oxide (NO) and NO/endothelin-1 ratio. In addition, the level of serum UA had significant positive correlations with serum malonaldehyde, serum C-reactive protein, serum oxidatively-modified low-density lipoprotein and serum low-density lipoprotein, but a negative correlation with serum superoxide dismutase.

Conclusions: Endothelial dysfunction in the CKD group was significant and had a positive correlation with the level of serum UA. Endothelial dysfunction in early CKD with hyperuricemia is perhaps related to oxidative stress, micro-inflammation and lipid oxidation.

Figure 2: Pathological images of rat arteries from groups A, B, and C. (A) Endothelial cells arranged in order under the vascular intima of group A (×400). (B) There was no obvious proliferation of medial smooth muscle cells in the vascular wall of group A (×200). (C) The morphology of endothelial cells of group B was slightly abnormal (×400). (D) There was no obvious proliferation of medial smooth muscle cells in the vascular wall of group B (×200). (E) Endothelial cells of group C had a foam-like change (×400). (F) Endothelial cells of group C shed from the vessel wall (×400). (G, H) Inflammatory cells accumulated in the vascular intima of group C (×400). (I) Neutrophil granulocytes were seen around the endothelial cells of group C (×400). (J) Mononuclear cells were seen around the endothelial cells of group C (×400). (K) Smooth muscle cells of group C proliferated, thickened, and had no order (×200).

Mentions:
In the light microscope, endothelial cells of group A were arranged closely under the vascular intima and inflammatory cells did not accumulate in the vascular wall (Figure 2A); smooth muscle cells were arranged in order with a spindle shape and an almost uniform morphology (Figure 2B). However, in group C, a foam-like interstitial edema of endothelial cells was visible (Figure 2E). Partial endothelial cells was shed from the vessel wall and the gap between them was broadened (Figure 2F). Further, inflammatory cells accumulated in the vascular intima (Figure 2G,H) and several inflammatory cells infiltrated within the membrane (Figure 2I,J). The thickness of the blood vessel wall increased. Medial smooth muscle cells proliferated and thickened with an irregular shape and a disordered arrangement (Figure 2K). The pathological change of the right-side nephrectomy group (group B) was similar to the experimental group, but less marked (Figure 2C). Smooth muscle cell proliferation was not obvious and it was well arranged (Figure 2D). The results confirmed significant vascular injury in the experimental group.

Figure 2: Pathological images of rat arteries from groups A, B, and C. (A) Endothelial cells arranged in order under the vascular intima of group A (×400). (B) There was no obvious proliferation of medial smooth muscle cells in the vascular wall of group A (×200). (C) The morphology of endothelial cells of group B was slightly abnormal (×400). (D) There was no obvious proliferation of medial smooth muscle cells in the vascular wall of group B (×200). (E) Endothelial cells of group C had a foam-like change (×400). (F) Endothelial cells of group C shed from the vessel wall (×400). (G, H) Inflammatory cells accumulated in the vascular intima of group C (×400). (I) Neutrophil granulocytes were seen around the endothelial cells of group C (×400). (J) Mononuclear cells were seen around the endothelial cells of group C (×400). (K) Smooth muscle cells of group C proliferated, thickened, and had no order (×200).

Mentions:
In the light microscope, endothelial cells of group A were arranged closely under the vascular intima and inflammatory cells did not accumulate in the vascular wall (Figure 2A); smooth muscle cells were arranged in order with a spindle shape and an almost uniform morphology (Figure 2B). However, in group C, a foam-like interstitial edema of endothelial cells was visible (Figure 2E). Partial endothelial cells was shed from the vessel wall and the gap between them was broadened (Figure 2F). Further, inflammatory cells accumulated in the vascular intima (Figure 2G,H) and several inflammatory cells infiltrated within the membrane (Figure 2I,J). The thickness of the blood vessel wall increased. Medial smooth muscle cells proliferated and thickened with an irregular shape and a disordered arrangement (Figure 2K). The pathological change of the right-side nephrectomy group (group B) was similar to the experimental group, but less marked (Figure 2C). Smooth muscle cell proliferation was not obvious and it was well arranged (Figure 2D). The results confirmed significant vascular injury in the experimental group.

Bottom Line:
An increase in serum uric acid (UA) occurs during the early and middle stages of chronic kidney disease (CKD) and aggravates the deterioration of kidney function.Linear regression analysis showed that the level of serum UA had a significant positive correlation with serum endothelin-1 and the percentage of collagen I positive area, but a negative correlation with serum nitric oxide (NO) and NO/endothelin-1 ratio.In addition, the level of serum UA had significant positive correlations with serum malonaldehyde, serum C-reactive protein, serum oxidatively-modified low-density lipoprotein and serum low-density lipoprotein, but a negative correlation with serum superoxide dismutase.

Background: An increase in serum uric acid (UA) occurs during the early and middle stages of chronic kidney disease (CKD) and aggravates the deterioration of kidney function. This study aims to explore the relation between UA and endothelial dysfunction in early CKD and its mechanisms in a murine model.

Methods: The experimental animals were randomly divided into three groups (n = 10): sham-operation group (control group), right nephrectomy only group (CKD group) and right nephrectomy with oxonic potassium group (CKD with hyperuricemia group). Furthermore, we analyzed the relation between UA and endothelial dysfunction indices in early CKD as well as its mechanisms.

Results: Linear regression analysis showed that the level of serum UA had a significant positive correlation with serum endothelin-1 and the percentage of collagen I positive area, but a negative correlation with serum nitric oxide (NO) and NO/endothelin-1 ratio. In addition, the level of serum UA had significant positive correlations with serum malonaldehyde, serum C-reactive protein, serum oxidatively-modified low-density lipoprotein and serum low-density lipoprotein, but a negative correlation with serum superoxide dismutase.

Conclusions: Endothelial dysfunction in the CKD group was significant and had a positive correlation with the level of serum UA. Endothelial dysfunction in early CKD with hyperuricemia is perhaps related to oxidative stress, micro-inflammation and lipid oxidation.